The ortho esters defined by structure (I) are useful water scavengers in organic reaction and solvents. The ortho esters can be used to generate an anyhdrous medium for reactions or other processes where the presence of water can be a detriment. The 1,1-dialkoxycycloalkanes defined by structure (II) can be used as protective or blocking structures for the alcohols corresponding to the alkoxy groups. The alcohols can be regenerated under acidic conditions. The compounds defined by structures (I) or (II) are also useful intermediates in the manufacture of pharmaceutical, photographic or agricultural products.
In the process of the invention, compounds of the structure (I) are prepared by first preparing an imino ether hydrochloride by reacting hydrogen cyanide with a secondary alkanol and hydrogen chloride in the presence of an inert organic solvent. Compounds of structure (I) are then prepared by further addition of secondary alkanol to the reaction mixture. Compounds of structure (II) are prepared by the addition of a cycloalkanone and secondary alkanol to the reaction mixture containing the imino ether hydrochloride.
It is known that when an organic acid nitrile is reacted with a primary alcohol and hydrogen chloride, imino ether hydrochloride is formed. This reaction scheme, generally known as the "Pinner" reaction, involves two steps for the preparation of ortho esters. First, an organic acid nitrile, primary alcohol and hydrogen chloride are reacted to prepare an imino ether hydrochloride. Second, the imino ether hydrochloride is separated from the reaction mixture by crystallization, washed for purification, and subsequently subjected to alcoholysis with additional primary alcohol to afford the ortho ester.
Thus, the Pinner reaction is discontinuous by virtue of the purification step and expensive because of the large amount of solvent required. Without the purification step, however, the ortho ester is not formed to a significant extent. Further, in this process, the yield of the ortho ester obtained fluctuates. The ortho ester of the primary alcohol thus obtained can be reacted with a a secondary alcohol in the presence of an acid catalyst to obtain the ortho ester of structure (I).
In the method of the invention, however, the preparation of orthoesters of structure (I) is continuous because the purification and transesterification steps are removed. The ortho ester obtained consistently exceeds 70% in yield and 99% in purity.
It is also known that 1,1-dialkoxycycloalkanes can be prepared by reacting cycloalkanones with alcohols in the presence of an acid catalyst. The present invention provides a novel method: cycloalkanone and secondary alkanol are added to a reaction mixture in which an imino ether hydrochloride has been produced.